Page 1758 - Williams Hematology ( PDFDrive )

1733

CHAPTER 107 is more sensitive than the bone survey, can identify early bone disease and

MYELOMA extramedullary disease, and can distinguish myeloma from normal marrow,
helping in quantifying the extent of the disease. Positron emission tomogra-
phy coupled with computed tomography (PET-CT) detects metabolically active
intramedullary or extramedullary myeloma foci and lytic bone lesions. The
Elizabeth O’Donnell, Francesca Cottini, Noopur Raje, most common staging system for myeloma is the International Staging Sys-
and Kenneth Anderson tem, based on two parameters, serum β -microglobulin (β M) and albumin;
2
2
three stages are defined and correlate with patient outcome. Serum levels of
β M, C-reactive protein, number of circulating plasma cells and their label-
2
SUMMARY ing-index are related to patient prognosis. Other prognostic factors include
the presence of specific chromosomal abnormalities (deletion of chromosome
Myeloma derives from the proliferation of a clone of malignant plasma cells 17p and loss of chromosome 1p/gain of chromosome 1q), altered gene expres-
that secretes a complete and/or partial monoclonal immunoglobulin protein. sion profiling, as well as MRI and PET-CT abnormalities. The introduction of
It originates in most, perhaps all, cases from an antecedent monoclonal gam- the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide and the
mopathy (essential monoclonal gammopathy) that progresses by clonal evo- proteasome inhibitor bortezomib have increased the 5-year relative survival
lution (acquisition of additional mutations) to a malignant B-cell malignancy, rate to 45 percent, with some patients achieving long-term survival of more
often myeloma, at a rate of 1 percent per year. Myeloma cells accumulate in than 10 years. Melphalan-based autologous hematopoietic stem cell trans-
the marrow microenvironment where contact with extracellular matrix and plantation in combination with novel agents can achieve remarkable results in
interaction with marrow accessory cells, such as osteoblasts, osteoclasts, and patients with good risk myeloma; patients who are not eligible for autologous
stromal cells, evokes cell growth and cell-survival signals, and contributes to transplant have traditionally been treated with melphalan and prednisone;
resistance to therapy. Myeloma cells show a complex genomic phenotype, novel agents such as bortezomib and lenalidomide are also active and well-
with chromosomal translocations and small copy number variations that affect tolerated also in this population. Consolidation and maintenance regimens
patient prognosis. Patients with myeloma have signs resulting from marrow based on lenalidomide as single agent or in combination with bortezomib
infiltration (anemia), bone destruction (bone pain, pathologic fractures), have been evaluated to extend the duration of complete remission following
excessive immunoglobulin production and deposition (renal failure and amy- autologous stem cell transplant. Finally, several novel agents can be used in
loidosis-related symptoms), and immunosuppression (e.g., infection). Clinical the setting of relapsed/refractory disease including new proteasome inhibi-
manifestations of myeloma vary as a result of the heterogeneous biology, tors (carfilzomib, ixazomib, and marizomib), IMiDs (pomalidomide), histone
spanning the entire spectrum from indolent to highly aggressive disease with deacetylase inhibitors (vorinostat, panabinostat, and ricolinostat), and mono-
extramedullary features. Diagnostic workup of myeloma should include serum clonal antibodies (daratumumab and elotuzumab).
protein electrophoresis together with immunoglobulin immunofixation,
serum-free light-chain assay, a 24-hour urine collection to quantitate urinary
protein, basic blood metabolic panel including blood counts and renal func-
tion, and marrow aspirate or biopsy with fluorescence in situ hybridization and DEFINITION AND HISTORY
cytogenetic studies. Radiographic bone survey is used to detect osteopenia Myeloma is a disease characterized by clonal expansion of malignant
and bone lesions or impending fractures. Magnetic resonance imaging (MRI) plasma cells that accumulate in the marrow, leading to anemia and
associated cytopenias, hypogammaglobulinemia, osteolytic bone dis-
ease, hypercalcemia, and renal dysfunction. Symptoms are a result of
1
tumor mass effects, cytokine release by myeloma cells, marrow stroma
Acronyms and Abbreviations: auto-HSCT, autologous hematopoietic stem cell or bone cells, or deposition of myeloma proteins into target organs
transplantation; BMSCs, bone marrow stromal cells; β M, β -microglobulin; CALGB, (amyloid light-chain [AL] amyloidosis and light-chain deposition dis-
2
2
Cancer and Leukemia Group B; CR, complete response; CRD, carfilzomib, lenalido- ease [LCDD]). Myeloma is part of a spectrum of diseases called plasma
mide, and dexamethasone; CT, computed tomography; CyBorD, cyclophosphamide, cell dyscrasias that include the following conditions: essential mono-
bortezomib, and dexamethasone; del, deletion; DLI, donor lymphocyte infusion; clonal gammopathy (MG; also known as monoclonal gammopathy
EBMT, European Bone Marrow Transplant Group; ECM, extracellular matrix; ECOG, of undetermined significance [MGUS]), smoldering myeloma (Chap.
Eastern Cooperative Oncology Group; EFS, event-free survival; EMP, extramedullary 106); solitary plasmacytoma, located in the bone as isolated lytic lesion
plasmacytoma; FISH, fluorescence in situ hybridization; GVHD, graft-versus-host or in the soft tissues; macroglobulinemia (Chap. 109); AL amyloidosis
disease; GVM, graft-versus-myeloma effect; IGF-1, insulin-like growth factor; ISS, and LCDD (Chap. 108); and very rare disorders, such as osteosclerotic
International Staging System; LCDD, light-chain deposition disease; MG, essential myeloma (POEMS [polyneuropathy, organomegaly, endocrinopathy, M
monoclonal gammopathy; MGUS, monoclonal gammopathy of undetermined sig- protein, and skin changes] syndrome), Castleman disease, and heavy
nificance; MIP, macrophage inflammatory protein; MP, melphalan-prednisone; MRD, chain diseases (α-heavy-chain disease, μ-heavy-chain disease, and
minimal residual disease; MRI, magnetic resonance imaging; MTD, maximum tol- γ-heavy chain disease) (Chap. 110). Myeloma derives from cells with
erated dose; ONJ, osteonecrosis of the jaw; ORR, overall response rate; OS, overall plasma cell morphologic features, capable of producing immunoglob-
survival; PET, positron emission tomography; RVD, lenalidomide, bortezomib, and ulin molecules (Chap. 75), which can be detected in the serum and/or
dexamethasone; SCID, severe combined immunodeficiency; sCR, stringent complete urine by electrophoresis and immunofixation. By definition, plasma cell
response; SMM, smoldering multiple myeloma; SOP, solitary osseous plasmacytoma; dyscrasias result from the expansion of monoclonal cells, with resul-
TGF-β, transforming growth factor-β; TTP, thrombotic thrombocytopenic purpura; tant monoclonal protein secretion; however, oligoclonal and polyclonal
VGPR, very good partial response; VTE, venous thromboembolism. protein abnormalities accompany some conditions, such as Castleman
disease.

Kaushansky_chapter 107_p1733-1772.indd 1733 9/21/15 12:33 PM